The association between alcohol consumption and colorectal carcinogenesis is partially mediated by the gut microbiome

BackgroundAlcohol consumption is one of the major risk factors of colorectal cancer (CRC). However, the mechanisms underlying this relationship are not fully understood, particularly the potential role of gut microbes. ObjectiveTo study associations of alcohol intake with the gut microbiome and colorectal lesions among CRC screening participants. Of particular interest was the potential role of gut microbes in mediating the association between alcohol intake and colorectal lesions. MethodsParticipants included fecal immunochemical test-positive women and men enrolled in the CRCbiome study, aged 55-77 years at inclusion. Intake of alcohol was assessed using a validated, semi-quantitative food frequency questionnaire. Integrating with shotgun metagenome based taxonomic and functional profiles, we studied associations with screen-detected colorectal lesions. The potential role of alcohol-associated gut microbes in mediating the association between alcohol intake and colorectal lesions was examined using causal mediation analysis. ResultsOf 1,468 participants with dietary data, 414 were diagnosed with advanced lesions (advanced adenoma, advanced serrated lesions or CRC). Alcohol intake was positively associated with advanced lesions in a dose-dependent manner (ptrend = 0.008), with odds ratio of 1.09 (95% confidence interval, 1.00, 1.19) per 10 g/day increase. Compared to non-consumers, those consuming alcohol were characterized by a distinct microbial profile, manifested as modest, but consistent, shifts in - and {beta}-diversity, and differentially abundant bacteria (Log2 fold change (Log2FC) >0: B. finegoldii and L. asaccharolyticus; Log2FC <0: S. mutans, B. dentinum, C. symbiosum and E. boltae). A causal mediation analysis showed that 12% of the association between alcohol intake and advanced lesions was mediated by alcohol-associated gut bacteria. ConclusionsAlcohol consumption was associated with a distinct microbial profile, which partly explained the association between alcohol intake and advanced colorectal lesions. Trial RegistrationThe BCSN is registered at clinicaltrials.gov (National clinical trial (NCT) no. 01538550).